ArticleScientific reports2016
A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Fragment-Based Discovery of Potent RNA-Competitive Inhibitors of the DEAH-Box RNA Helicase DHX8.Journal of medicinal chemistry · 2026Article
- Article
- Specific radiation damage to halogenated inhibitors and ligands in protein-ligand crystal structures.Journal of applied crystallography · 2024Article
- Flavonoids Regulate Redox-Responsive Transcription Factors in Glioblastoma and Microglia.Cells · 2023Article
- Exploring the Anticancer Potential ofPlants (Basel, Switzerland) · 2023Article
- Network pharmacology and experimental validation to reveal the target of matrine against PRRSV.iScience · 2023Article
- Discovery and Characterization of a Cryptic Secondary Binding Site in the Molecular Chaperone HSP70.Molecules (Basel, Switzerland) · 2022Article
- A non-traditional crystal-based compound screening method targeting the ATP binding site ofFrontiers in molecular biosciences · 2022Article
- Unravelling the Interaction of Piperlongumine with the Nucleotide-Binding Domain of HSP70: A Spectroscopic and In Silico Study.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Detailed Characterization of the Cooperative Binding of Piperine with Heat Shock Protein 70 by Molecular Biophysical Approaches.Biomedicines · 2020Article
- HSP70 Multi-Functionality in Cancer.Cells · 2020Review
- Kinetic Optimization of Lysine-Targeting Covalent Inhibitors of HSP72.Journal of medicinal chemistry · 2019Article
- Establishing Computational Approaches Towards Identifying Malarial Allosteric Modulators: A Case Study ofInternational journal of molecular sciences · 2019Article
- HSPA8/HSC70 in Immune Disorders: A Molecular Rheostat that Adjusts Chaperone-Mediated Autophagy Substrates.Cells · 2019Review
- Discorhabdin N, a South African Natural Compound, for Hsp72 and Hsc70 Allosteric Modulation: Combined Study of Molecular Modeling and Dynamic Residue Network Analysis.Molecules (Basel, Switzerland) · 2019Article
- Choose and Use Your Chemical Probe Wisely to Explore Cancer Biology.Cancer cell · 2017Review
- Repurposing p97 inhibitors for chemical modulation of the bacterial ClpB-DnaK bichaperone system.The Journal of biological chemistryArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
The heat shock protein 70s (HSP70s) are molecular chaperones implicated in many cancers and of significant interest as targets for novel cancer therapies. Several HSP70 inhibitors have been reported, but because the majority have poor physicochemical properties and for many the exact mode of action is poorly understood, more detailed mechanistic and structural insight into ligand-binding to HSP70s is urgently needed. Here we describe the first comprehensive fragment-based inhibitor exploration of an HSP70 enzyme, which yielded an amino-quinazoline fragment that was elaborated to a novel ATP binding site ligand with different physicochemical properties to known adenosine-based HSP70 inhibitors. Crystal structures of amino-quinazoline ligands bound to the different conformational states of the HSP70 nucleotide binding domain highlighted the challenges of a fragment-based approach when applied to this particular flexible enzyme class with an ATP-binding site that changes shape and size during its catalytic cycle. In these studies we showed that Ser275 is a key residue in the selective binding of ATP. Additionally, the structural data revealed a potential functional role for the ATP ribose moiety in priming the protein for the formation of the ATP-bound pre-hydrolysis complex by influencing the conformation of one of the phosphate binding loops.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.